Malaria elimination or eradication efforts are underway and strategies such as new drugs, vaccines and vector control techniques, are being implemented to reduce and even eliminate the health burden of malaria. Anti-malarial drug treatment is an essential part of all malaria control programs, and drug resistance is a major factor that may undermine these efforts to control malaria. To prevent or limit the effect of emerging drug resistance it will be critical to monitor the effectiveness of available anti-malarial drugs, as well as evaluate new safe and economical drugs that are active against drug resistant parasites. Successful eradication of malaria will require careful assessment of current levels of drug resistance and clinical responses to drug treatments, as well as development of simple methods to assess drug resistance and response levels more broadly across malaria endemic regions. This will require the development of tools to monitor drug responses and detect changes in the parasite population in response to current or future drug applications. Prolonged application of incompletely effective chemotherapeutic treatments thus leads to the spread and fixation of drug resistance alleles in areas where malaria is endemic. New drugs or new combinations of drugs, including Artemisinin Combination Therapies (ACTs) and use of Intermittent Preventive Treatment in pregnancy (IPTp), have been introduced to reduce and perhaps ultimately eliminate the disease burden of malaria. In this proposal we will assess the current level of drug resistance to ACTs and the effectiveness of IPTp treatment in four sentinel sites in West Africa. We will characterize the drug responses of parasites currently causing malaria infection in these sites, and use population genetic approaches to discover genetic markers associated with these resistant parasites. From these data we will identify novel molecular markers that will be validated and tested for their role in drug resistance and their utility for identification of drug resistant parasites in patients. Development of simple and reliable genotyping assays for these markers will then enable clinicians and researchers to identify and track parasites that are likely to fail drug treatment and compromise malaria control strategies.